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Biomedical subjects

H Oka

Publications and source records attributed to H Oka.

At least 199 records · Page 11Linked to original sources

[A successful case of repeated prosthetic valve re-replacement for somatic growth in childhood].

The patient who had had systemic atrio-ventricular valve replacement with Björk-Shiley 19 M at the age of 4 years was treated successfully with repeated re-replacement with St. Jude Medical 23M and St. Jude Medical 27M at the age of 8 years and 16 years respectively, because of his somatic growth. Two size larger valve was easily replaced at each operation. The original disease of this patient was corrected transposition of the great arteries with ventricular septal defect and regurgitation of the left atrio-ventricular valve caused by Ebstain anomaly and severe pulmonary hypertension. This case revealed that the annulus of the atrio-ventricular valve would grow even when fixed to the prosthetic valve sawing ring, thereby permitting the use of a larger-sized valve at the time of second and third prosthetic valve re-replacement.

Adolescent↗

[Intracranial extracerebral glioma].

A case of solitary leptomeningeal extracerebral glioma is reported. A 75-year-old man was admitted to our hospital because of headache and right hemiparesis. CT scan and carotid angiography revealed a tumor in the left convexity. At operation, the tumor was located between the dura mater and the arachnoid membrane and adhered to the brain surface only in a limited area. Histological study including immunostain and electron microscopy showed the tumor as anaplastic oligo-astrocytoma. We speculate that our case may originate from a heterotopic glial nest in the dural border cell layer of dura mater. This explanation seems likely because the tumor was located mostly in the subdural space.

Aged↗

[Completely thrombosed large aneurysm of the distal middle cerebral artery: a case report].

A 19 year old male was admitted for evaluation after a seizure. Physical and neurological examination was normal. CT demonstrated an enlarged, high density mass in the right parietal lobe. MRI showed a homogeneous high intensity T1 weighted mass, surrounded by a low intensity T2 weighted rim in the right parietal lobe. Angiography did not show any abnormal findings. A diagnosis of cavernous angioma with primary bleeding in the subcortical region of the right parietal lobe was made after radiological examination. Histological examination showed a completely thrombosed aneurysm. The mechanism of the complete thrombosis and the growth of this large aneurysm and the shortcomings of radiological examination are discussed.

Adult↗

[The managements of nutrition for hepatic cirrhosis].

Hepatic cirrhosis is the end stage in chronic liver diseases and this condition cause the patient's death because of hepatic failure. A prognosis of patients with hepatic cirrhosis depend on the liver function, especially the function of mass of residual hepatocytes and this function expressed by level of serum albumin, cholinesterase (Ch E) or ICGR-15. This function is improved a management of nutrition because hepatocytes are regenerate by intake of protein. In compensated hepatic cirrhosis, hepatocytes are regenerate by dietary intake of 100-120 g/day of protein and the function of mass of residual hepatocytes is increased. The prognosis of these patients with compensated hepatic cirrhosis are improved by this management of nutrition.

Dietary Proteins↗

Immunohistochemical detection of alpha-catenin expression in human cancers.

The function of E-cadherin is thought to be regulated by its associated cytoplasmic proteins including alpha-catenin. To determine whether possible downregulation of alpha-catenin expression may play a role in tumor invasion and metastasis through the dysfunction of E-cadherin, we investigated the expression of alpha-catenin in human carcinoma samples (esophagus, stomach, and colon) by immunohistochemistry using our monoclonal antibody against alpha-catenin (alpha-18). Normal epithelium expressed alpha-catenin strongly without exception. However, alpha-catenin expression was frequently reduced in primary tumors of esophagus (12 of 15:80%), stomach (14 of 20: 70%), and colon (8 of 10: 80%). Of the tumors with reduced alpha-catenin expression, alpha-catenin expression was completely negative in 70.6% of them (9 of 12 in esophagus, 9 of 14 in stomach, and 6 of 8 in colon). These results also suggested that some human cancer cells may have impaired E-cadherin-mediated cell adhesiveness through the downregulation of alpha-catenin expression.

Adenocarcinoma↗

Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector.

Adeno-associated virus (AAV) vectors expressing the normal cystic fibrosis transmembrane conductance regulator (CFTR) cDNA complement the cystic fibrosis (CF) defect in vitro. Unlike other DNA virus vectors, AAV is a stably integrating virus, which could make possible long-term in vivo complementation of the CF defect in the airway epithelium. We report AAV-CFTR gene transfer and expression after infection of primary CF nasal polyp cells and after in vivo delivery of AAV-CFTR vector to one lobe of the rabbit lung through a fiberoptic bronchoscope. In the rabbit, vector DNA could be detected in the infected lobe up to 6 months after administration. A 26-amino acid polypeptide sequence unique to the recombinant AAV-CFTR protein was used to generate both oligonucleotide probes and a polyclonal antibody which allowed the unambiguous identification of vector RNA and CFTR protein expression. With these reagents, CFTR RNA and protein were detected in the airway epithelium of the infected lobe for up to 6 months after vector administration. AAV vectors do, therefore, efficiently promote in vivo gene transfer to the airway epithelium which is stable over several months. These findings indicate that AAV-CFTR vectors could potentially be very useful for gene therapy.

Amino Acid Sequence↗

Modulation of T cell production of interferon-gamma by human monocytes: effect of engagement of CD14 on monocytes.

It has been suggested that CD14 might have influences on a variety of immunoregulatory functions of monocytes. The current studies therefore examined in detail the immunoregulatory roles of CD14 by studying the effects of anti-CD14 mAb. Anti-CD14 mAb suppressed the monocyte-dependent interferon-gamma (IFN-gamma) production by CD4+ T cells induced by soluble anti-CD3. Although anti-CD14 mAb also suppressed the IL-6 production by monocytes, the inhibition of the IFN-gamma production induced by soluble anti-CD3 was not restored by addition of exogenous IL-6 or factors generated from cultured monocytes. Of note, anti-CD14 mAb decreased the expression of CD54, but not that of CD11a or CD18, on monocytes, suggesting that inhibition of the soluble anti-CD3-induced IFN-gamma production by anti-CD14 mAb might be a result from decrease in CD11a/CD18-CD54-mediated interactions between CD4+ T cells and monocytes. By contrast, anti-CD14 mAb enhanced the IFN-gamma production by immobilized anti-CD3-activated CD4+ T cells in the presence of monocytes. This enhancement of the IFN-gamma production required physical contact between monocytes and T cells, which does not involve MHC class II antigen-CD4 interactions. These results indicate that CD14 on monocytes plays a variety of immunomodulatory functions depending upon the nature of stimulation. The data thus demonstrated the presence of several different interactions between monocytes and T cells that regulate the T cell cytokine production.

Antibodies, Monoclonal↗

Growth-regulatory mechanism of two human esophageal-cancer cell lines in protein-free conditions.

We investigated the growth-regulatory mechanism of 2 esophageal squamous-cancer cell lines, TE2-NS and TE3-OS cells, both of which can grow stably in protein-free conditions in vitro. Protein-free conditioned media from TE2-NS and TE3-OS cells stimulated the growth of these cells. Exogenous epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), insulin-like growth factor (IGF)-I and -II enhanced cell proliferation by 2.2- to 3.8-fold in protein-free conditions, as compared with an untreated control. Receptor-binding assays showed that both TE2-NS and TE3-OS cells possessed a single class of high-affinity binding sites for IGF-I and 2 classes of binding sites for TGF-alpha, as confirmed on the cell membrane by immunochemistry. These results suggest that EGF, TGF-alpha and IGFs are candidates for the autocrine growth factor in cancer cells. The addition of inhibitory monoclonal antibodies against TGF-alpha and EGFR, but not those against either EGF or IGF-IR, significantly inhibited growth of the cells. Immunocytochemical staining and ELISA of the conditioned media both confirmed the production of TGF-alpha protein, but not EGF protein, in these cell lines. The data for a protein-free culture system strongly suggested that TGF-alpha, but not EGF or IGF, is biologically important as an autocrine growth factor in the growth of these cell lines in vitro.

Antibodies, Monoclonal↗

Prognostic value of DNA ploidy in squamous cell carcinoma of esophagus. Analyzed with improved flow cytometric measurement.

BACKGROUND: The prognostic value of flow cytometric DNA analysis on paraffin-embedded tumor samples has been controversial in esophageal cancer. To clarify its true significance, the authors developed an improved method that excludes the possibility of contamination by lymphocytes in tumor sample. METHODS: Single nuclear suspension was prepared from paraffin-embedded samples on 103 patients with squamous cell carcinoma of the esophagus. Both DNA content and nuclear size were simultaneously measured by flow cytometry on 30,000 nuclei, and contaminated lymphocyte nuclei were eliminated from the data by optimal gating. Correlation between DNA ploidy and postoperative survival was examined. RESULTS: Analysis using a flow cytometric cell sorter showed that the frequency of tumor cells in the lymphocyte-reducing gating fraction (LGF) was significantly higher than that in the conventional nongating fraction (NGF). LGF analysis showed aneuploid peaks in 58 patients (56.3%), but NGF analysis showed aneuploid peaks in only 38 patients. LGF analysis revealed that the aneuploid tumors had higher histologic grading (P < 0.05) and worse survival rate (P < 0.01) compared with diploid tumors. However, conventional methods could not detect this difference. CONCLUSIONS: Flow cytometric analysis gating by nuclear size may be helpful to detect aneuploid peaks, and for predicting prognosis of patients with squamous cell carcinoma of esophagus.

Adult↗

Congenital histidine-rich glycoprotein deficiency.

The proband, a 43-year-old woman, suffered from right transverse sinus thrombosis during oral contraceptive treatment. A month after stopping the drug, her plasma activities of antithrombin III, protein C, protein S, heparin cofactor II, plasminogen and plasminogen activator inhibitor were normal, but her plasma histidine-rich glycoprotein (HRG) level was only 21% of the normal level of 109.5 +/- 51.5% (mean +/- 2 SD). The HRG concentrations in her plasma determined on four different occasions over 6 months were similar. She showed no clinical signs of liver insufficiency or sepsis. Low levels of plasma HRG (20% to 35% of normal) were also found in her aunt, uncle and two daughters. These results suggest that congenital HRG deficiency is inheritary in this family.

Adult↗

Correlation between E-cadherin expression and invasiveness in vitro in a human esophageal cancer cell line.

E-cadherin, a member of the cadherin family, plays a major role in cell-cell adhesion of normal epithelium. Recent studies have shown that reduction or loss of E-cadherin expression in carcinomas have some relationship with their clinicopathological manifestation including invasion and metastasis. In the present study, we have established cell clones with different E-cadherin expression from human esophageal cancer, TE-2, and examined their adhesive capacity and invasiveness in vitro. Cell clones with positive E-cadherin expression [ECD(+) cells] were round and formed cobblestone colonies, while cell clones negative for E-cadherin [ECD(-) cells] had spindle shapes and formed dispersed colonies. ECD(+) cells showed higher adhesive capacity than ECD(-) cells, in both an aggregation assay with gyratory shaking culture and a dissociation assay of cells passing through the micropore membrane. Monoclonal antibody against human E-cadherin (HECD1) effectively diminished the mutual adhesion of ECD(+) cells but did not affect that of ECD(-) cells. Tumor invasiveness was evaluated with organotypic raft culture which is a coculture system consisting of two layers, a collagen gel layer containing fibroblasts and overlying reconstituted stratified squamous epithelium. ECD(+) cells formed complete stratified epithelium, but ECD(-) cells did not. ECD(+) cells did not invade the collagen/fibroblast gel, but ECD(-) cells did. Furthermore, ECD(+) cells showed invasion when an antibody against E-cadherin was used. Thus, loss or dysfunction of E-cadherin diminishes intercellular adhesion and results in the acquisition of invasive capacity in the cell line we examined.

Actins↗

Prognostic significance of transforming growth factor-alpha in human esophageal carcinoma. Implication for the autocrine proliferation.

BACKGROUND: The authors recently used immunostaining to demonstrate that patients with epidermal growth factor receptor (EGFR) overexpression have poor survival after surgery. However, the clinical significance of transforming growth factor (TGF)-alpha, one of the ligands of EGFR, has not been demonstrated in esophageal carcinoma. METHODS: Immunohistochemical study for TGF-alpha and EGFR was performed on 57 esophageal squamous cell carcinomas using monoclonal antibodies. RESULTS: TGF-alpha expression was positive in 35% of the tumors, and EGFR overexpression, defined as stronger staining in cancer cells than in normal epithelium, was positive in 43% of the tumors, according to the authors' arbitrary criteria. The incidence of TGF-alpha positivity was relatively higher in patients with the EGFR overexpression (EGFR+) than in the patients with non-overexpression (EGFR-). The survival rate was significantly lower in patients with TGF-alpha(+) than in those with TGF-alpha(-) (P < 0.01) and in patients with EGFR(+) than in patients with EGFR(-) (P < 0.01), respectively. Considering TGF-alpha and EGFR expression simultaneously, the survival rate of the patients with TGF-alpha(+)/EGFR(+) tumors was the lowest of the four subgroups, with statistically significant differences noted. These relationships between the immunoreactivities and survival curves were observed in the analysis within patients with node-positive disease. In addition, a multivariate statistical analysis demonstrated that TGF-alpha was the only significant variable, whereas EGFR and nodal status provided no additional information regarding postoperative survival. CONCLUSION: The results presented suggest that TGF-alpha may act as an autocrine growth factor through hyperproducing EGFR and that its expression and EGFR overexpression may prove useful as a valuable prognostic indicator for patients with esophageal carcinoma.

Carcinoma, Squamous Cell↗

Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis.

E-cadherin (E-cad) is a subclass of the cadherin family that plays a major role in maintenance of intercellular junctions in epithelial tissues. In order to explore the correlation between the expression of E-cad and cancer invasion and metastasis in vivo, we performed an immunohistochemical examination for E-cad expression in 120 patients with breast cancer using our specific anti-E-cad monoclonal antibody. In noncancerous epithelial cells, E-cad was strongly expressed on cell-cell boundaries, whereas various staining patterns were observed in tumors. Of these 120 tumors, 56 (47%) showed Pr type expression of E-cad, and 64 (53%) showed Rd type or negative expression. We found significant correlations between E-cad expression and clinicopathological features. The frequency of Rd type was significantly higher in invasive ductal carcinomas (58%, 56 of 97) and poorly differentiated carcinomas (84%, 21 of 25) than in noninvasive and well-differentiated carcinomas. Furthermore, a high frequency of Rd type was detected in the following advanced tumors: T3,4 tumors, 71% (22 of 31); tumors with extensive lymph node metastasis, 74% (29 of 39); and tumors with distant metastasis, 86% (19 of 22). These values were significantly higher compared with their counterparts. The expression of epidermal growth factor receptor tended to be positive in E-cad-positive tumors. However, no significant relationship was seen among E-cad expression, menopausal status, hormone receptor status, and DNA ploidy pattern. These results suggest that the reduction of E-cad expression may play an important role in invasion and metastasis of human breast cancer.

Adult↗

Projections of the anterior coronal gyrus to the subthalamic nucleus in the cat: a combined retrograde and anterograde WGA-HRP study.

In order to re-examine the corticosubthalamic projections in the cat, WGA-HRP was injected into the subthalamic nucleus (STN). Following WGA-HRP injections into the lateral STN, a small number of retrogradely labeled neurons were found in the anterior coronal gyrus (ACG) as well as the anterior sigmoid gyrus. To confirm the projection of the ACG to the lateral STN, which had not been reported previously, WGA-HRP was injected into the ACG. Anterogradely labeled fiber terminals were found in the dorsolateral part of the STN. These results indicate that the ACG influences the STN activity through its direct projections.

Animals↗

Regulation of human B cell responsiveness by interferon-alpha: interferon-alpha-mediated suppression of B cell function is reversed through direct interactions between monocytes and B cells.

Previous studies have revealed that interferon-alpha (IFN-alpha) suppresses the B cell responses stimulated with Staphylococcus aureus (SA) + IL-2 in the complete absence of monocytes but enhances the responses of B cells contaminated with monocytes. The current studies therefore examined in detail the combined effects of IFN-alpha and monocytes on the B cell responses induced by SA + IL-2. Monocytes overcome the suppressive effects of IFN-alpha on the IgM production induced by SA + IL-2. Thus, in the presence of monocytes, IFN-alpha enhanced the IgM production by B cells stimulated with SA + IL-2. IFN-alpha still enhanced the IgM production induced by SA + IL-2 in the presence of monocytes and indomethacin. The IFN-alpha-mediated suppression of B cell responsiveness was not overcome by addition of factors generated from SA-activated monocytes, or any of IL-1 beta, IL-6, and TNF-alpha. Of note, the IFN-alpha-mediated suppression of B cell responsiveness was overcome only when B cells and monocytes were allowed to contact with each other. This reversal of the IFN-alpha-mediated suppression of B cell function was not blocked by any of the mAb to CD11a, CD18, CD54, or monomorphic determinants of HLA-DR. These results indicate that IFN-alpha enhances the B cell responses induced by SA + IL-2 through direct interactions between monocytes and B cells that do not involve lymphocyte-function-associated-1 molecules, intercellular adhesion molecule-1, or HLA-DR antigens. Thus, the data demonstrate the presence of unique direct interactions between B cells and monocytes that regulate human B cell responsiveness.

Adult↗